| Revision as of 12:33, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456658454 of page Raltitrexed for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 21:24, 14 July 2024 edit Jjamulla (talk | contribs)Extended confirmed users1,123 editsm fix bare URL |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 464379925 |
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| Verifiedfields = changed |
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| verifiedrevid = 417955154 |
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| IUPAC_name = ''N''-amino}-2-thienyl)carbonyl]-<small>L</small>-glutamic acid |
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| IUPAC_name = ''N''-amino}-2-thienyl)carbonyl]-<small>L</small>-glutamic acid |
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| image = Raltitrexed.svg |
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| image = Raltitrexed.svg |
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| image2 = Raltitrexed ball-and-stick.png |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_US = Not available <!-- OTC / Rx-only --> |
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| legal_status = Not available in U.S. |
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| legal_status = |
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| routes_of_administration = ] |
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| routes_of_administration = ] |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| bioavailability = |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = |
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| elimination_half-life = |
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| excretion = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| IUPHAR_ligand = 7403 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 112887-68-0 |
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| CAS_number = 112887-68-0 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = FCB9EGG971 |
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| UNII = FCB9EGG971 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D01064 |
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| KEGG = D01064 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 225071 |
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| ChEMBL = 225071 |
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| PDB_ligand = D16 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=21 | H=22 | N=4 | O=6 | S=1 |
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| C=21 | H=22 | N=4 | O=6 | S=1 |
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| molecular_weight = 458.489 g/mol |
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| smiles = O=C(c3sc(N(C)Cc2cc1C(=O)\N=C(/Nc1cc2)C)cc3)N(C(=O)O)CCC(=O)O |
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| smiles = O=C(c3sc(N(C)Cc2cc1C(=O)\N=C(/Nc1cc2)C)cc3)N(C(=O)O)CCC(=O)O |
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| InChI = 1/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1 |
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| InChIKey = IVTVGDXNLFLDRM-HNNXBMFYBV |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1 |
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| StdInChI = 1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1 |
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| StdInChIKey = IVTVGDXNLFLDRM-HNNXBMFYSA-N |
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| StdInChIKey = IVTVGDXNLFLDRM-HNNXBMFYSA-N |
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}} |
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}} |
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'''Raltitrexed''' (Thaltitrexed, Tomudex, TDX, ZD 1694) is an ] drug used in cancer ]. It is an ], and is manufactured by ].<ref>{{cite journal|vauthors=Widemann BC, Balis FM, Godwin KS, McCully C, Adamson PC|year=1999|title=The plasma pharmacokinetics and cerebrospinal fluid penetration of the thymidylate synthase inhibitor raltitrexed (Tomudex) in a nonhuman primate model|url=https://pubmed.ncbi.nlm.nih.gov/10550563/|journal=Cancer Chemother. Pharmacol.|volume=44|issue=6|pages=439–43|doi=10.1007/s002800051116|pmid=10550563|s2cid=9006510}}</ref> |
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==Uses== |
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Used in treatment of colorectal cancer since 1998, it may also be used in the treatment of malignant ].<ref name="raltitrexed">{{cite journal | pmid = 1256598 | volume=120 | title= | journal=Ned Tijdschr Geneeskd | pages=477 | vauthors=Zuidema PJ| issue=11 | year=1976 }}</ref> Raltitrexed is approved for use in Canada and some European countries, but is not approved by the US FDA.<ref>{{Cite web | url=https://www.medscape.com/viewarticle/584383_3 | title=Pharmacogenetics in Colorectal Cancer}}</ref><ref>{{Cite web | url=https://www.ema.europa.eu/en/documents/pip-decision/p/17/2009-european-medicines-agency-decision-27-january-2009-granting-product-specific-waiver-raltitrexed/2006-europe_en.pdf |title=EUROPEAN MEDICINES AGENCY DECISION on the granting of a product-specific waiver for raltitrexed (Tomudex) |publisher=European Medicines Agency |date=January 27, 2009}}</ref> |
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==Mechanism of action== |
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Raltitrexed is chemically similar to ] and is in the class of chemotherapy drugs called ]s, which inhibit one or more of three enzymes that use folate and derivatives as substrates: ], ] and ]. Raltitrexed is fully active after ], which allows cellular retention of the drug. |
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By inhibiting Thymidylate synthase (TS), thus formation of precursor pyrimidine nucleotides, raltitrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells. |
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Inhibition of ] cell growth in culture ] = 9 nM, is one of the strongest ]s in use. |
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Structure and phase I clinical trial of the precursor drug, CB3717, was described in 1986.<ref>{{cite journal |vauthors=Calvert AH, Alison DL, Harland SJ, etal |title=A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717 |journal=J. Clin. Oncol. |volume=4 |issue=8 |pages=1245–52 |date=August 1986 |pmid=3734849 |url=http://www.jco.org/cgi/pmidlookup?view=long&pmid=3734849|doi=10.1200/JCO.1986.4.8.1245 }}</ref> |
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==References== |
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{{reflist}} |
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{{Chemotherapeutic agents}} |
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] |
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] |
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